Opioid and Benzodiazepine Withdrawal Syndrome in PICU Patients: Which Risk Factors Matter?

Abstract

BACKGROUND AND AIMS:

Although iatrogenic withdrawal syndrome (IWS) has been recognized in patients exposed to opioids and benzodiazepines, very few studies have used a validated tool for diagnosis and assessment of IWS in critically ill children. We sought to determine IWS rate, risk factors, and outcomes of IWS patients.

METHODS:

Prospective observational study conducted in a pediatric intensive care unit. A total of 137 patients (31 with IWS and 106 with no IWS) received a continuous infusion of fentanyl and midazolam for 3 or more days. The Sophia Observation withdrawal Symptoms scale was repeatedly applied when children were weaned off sedation/analgesia.

RESULTS:

The overall incidence of IWS was 22.6%. Of the 31 IWS patients, 6 showed IWS with less than 5 days sedation or analgesia. Logistic regression showed that the median peak dose of midazolam was associated with IWS development (odds ratio 1.4). Receiver-operating curve showed a cut-off value of 0.35 mg/kg/h for midazolam peak dose (sensitivity 96.7%, specificity 51%, positive predictive value 36.6%, and negative predictive value 98.2%), with area under the curve of 0.80. IWS patients had a longer time on mechanical ventilation, prolonged pediatric intensive care unit, and hospital stays, and required prolonged period to have drugs discontinued.

CONCLUSIONS:

Although length of sedation/analgesia for at least5 days has been widely proposed for monitoring IWS, our data suggest that initiating monitoring after 3 sedation days is highly recommended. In addition, patients requiring infusion rates of midazolam above 0.35 mg/kg/h should be considered at high risk for IWS.

• Authors: Paulo Sérgio Lucas da Silva, Maria Eunice Reis, Thais Suelotto Machado Fonseca, Marcelo Cunio Machado Fonseca
• Journal: Journal of addiction medicine (J Addict Med) 2016 Mar-Apr Vol. 10 Issue 2 Pg. 110-6 ISSN: 1935-3227 [Electronic] United States
• PMID: 26927302 (Publication Type: Journal Article, Observational Study)

Chemical References

• Analgesics, Opioid
• Benzodiazepines
• Midazolam
• Fentanyl

Topics

• Adolescent
• Analgesics, Opioid (adverse effects)
• Benzodiazepines (adverse effects)
• Brazil (epidemiology)
• Child
• Child, Preschool
• Critical Care (methods)
• Female
• Fentanyl (adverse effects)
• Humans
• Iatrogenic Disease (epidemiology)
• Incidence
• Infant
• Intensive Care Units, Pediatric
• Male
• Midazolam (adverse effects)
• Prospective Studies
• Risk Factors
• Substance Withdrawal Syndrome (epidemiology)